Substance abuse and dependency are important problems facing societies all over the world. According to the World Drug Report 2008, about 5% of the world population uses illicit drugs and in 0.6% of the world population, drug use is a problem. In the United States, according to the Substance Abuse and Mental Health Services Administration's (SAMHSA's) National Survey on Drug Use and Health in 2006, 23.6 million persons aged 12 or older needed treatment for an illicit drug or alcohol abuse problem (9.6 percent of the persons aged 12 or older). Of these, only 2.5 million—10.8 percent of those who needed treatment—received it at a specialty facility. Substance abuse and dependency result in enormous loss of productive manpower all over the world and imposes costs on governments and societies in terms of treatment support, insurance payouts, and spending on prevention and de-addiction programs.
Optogenetics is the combination of genetic and optical methods used to control specific events in targeted cells of living tissue, even within freely moving mammals and other animals, with the temporal precision (millisecond-timescale) needed to keep pace with functioning intact biological systems. The hallmark of optogenetics is the introduction of fast light-responsive opsin channel or pump proteins to the plasma membranes of target neuronal cells that allow temporally precise manipulation of neuronal membrane potential while maintaining cell-type resolution through the use of specific targeting mechanisms. Among the microbial opsins which can be used to investigate the function of neural systems are the halorhodopsins (NpHRs), used to promote membrane hyperpolarization when illuminated. In just a few short years, the field of optogenetics has furthered the fundamental scientific understanding of how specific cell types contribute to the function of biological tissues such as neural circuits in vivo. Moreover, on the clinical side, optogenetics-driven research has led to insights into the neurological mechanisms underlying mammalian behavior.
In spite of these advances, the neurophysiological substrates underlying complex human behaviors, such as substance abuse and dependency (addiction) remain poorly understood, despite emerging information on the role that specific areas of the brain play in these behaviors. For example, the nucleus accumbens (NAc) is a collection of neurons that forms the main part of the ventral striatum. The NAc is thought to play an important role in reward, pleasure, laughter, addiction, aggression, fear, and the placebo effect. Acetylcholine is an important and widely studied neurotransmitter, which acts on a variety of receptors and target cells. Some in vivo pharmacological approaches have shown that cholinergic transmission in the NAc is required for reward learning behaviors. Cholinergic interneurons within the NAc are particularly intriguing because they constitute less than 1% of the local neural population, yet they project throughout the NAc and provide its only known cholinergic input. Relevant cholinergic receptors are expressed locally, and nicotinic and muscarinic pharmacological agonists can exert complex influences on medium spiny neurons (MSNs, which represent >95% of the local neuronal population and constitute the output of the NAc). However, the net effect (if any) of the cholinergic interneurons on any aspect of NAc physiology or reward-related behavior is unknown.
What is needed, therefore, is a tool which would permit investigation of the causal role played by cholinergic interneurons within the NAc in reward-related behaviors such as substance dependency. Understanding the neural pathways that underlie addiction may help aid in the discovery and screening of pharmacological therapies to treat patients with such disorders as well as open up the possibility of using such tools to disrupt these behaviors in the brains of drug-addicted individuals.
Throughout this specification, references are made to publications (e.g., scientific articles), patent applications, patents, etc., all of which are herein incorporated by reference in their entirety.